Preventive Nutrition and Food Science

  • 제9권1호
  • /
  • Pages.71-78
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  • 2004
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  • 2287-1098(pISSN)
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  • 2287-8602(eISSN)
한국식품영양과학회 (The Korean Society of Food Science and Nutrition)
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The Combined Effect of β2- and β3-Adrenergic Receptor Genotypes on Hyperglycemic Risk in the Korean Population

  • Oh, Hyun-Hee (Department of Medical R＆D, Korea Institute of Oriental Medicine) ;
  • Kim, Kil-Soo (Kirin Oriental Hospita) ;
  • Park, Sun-Mi (Department of Medical R＆D, Korea Institute of Oriental Medicin) ;
  • Shin, Seung-Uoo (Kirin Oriental Hospita) ;
  • Yang, Hun-Sung (Department of Medical R＆D, Korea Institute of Oriental Medicin) ;
  • Yoon, Yoo-Sik (Department of Medical R＆D, Korea Institute of Oriental Medicine)
  • 발행 : 2004.03.01
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초록

Adrenergic receptors play a major role in thermogenesis and lipolysis in brown and visceral adipose tissues, and have been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of $\beta$2-adrenergic receptor ($\beta$2AR) and $\beta$3-adrenergic receptor ($\beta$3AR) genotypes on hyperglycemia and obesity in the Korean population. A representative sample consisting of 530 Korean men and women were measured for height, weight, BMI, WHR, obesity index and body composition. The genotypes of $\beta$2AR polymorphism in codon 27 and $\beta$3AR polymorphism in codon 64 were analyzed by the PCR RFLP method. Serum concentrations of fasting glucose, total cholesterol, HDL cholesterol and triglyceride were determined. The frequencies of $\beta$2AR and $\beta$3AR genotype were: both wild type, 62.5% ; only $\beta$2AR variant type, 12.8% ; only $\beta$3AR variant type, 18.8% ; and both variant type, 5.8% ; the frequency of E and R alleles were 0.098 and 0.137, respectively. Among the physiological parameters, fasting glucose level was significantly higher in subjects with both variant type compared with the three other types (p <0.05), Subjects with both variant type had 12%, 12% and 9.3% increases in serum glucose levels compared with wild type, only $\beta$2AR variant type, and only $\beta$3AR variant type, respectively. When logistic regression analysis was conducted to estimate the risk for hyperglycemia, the subjects were selected for fasting blood glucose concentrations of more than 6.105 m㏖/L (110 mg/dL), and the odds ratios were 1.215 (p=0.636) for only $\beta$2AR variant type,1.659 (p=0.089) for only $\beta$3AR variant type, and 3.078 (p=0.011) for both variant type. These results suggest that the interaction of $\beta$2AR and $\beta$3AR variant genotypes has a strong association with increased glucose levels, and might be a significant risk factor for hyperglycemia among Korean subjects.

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참고문헌

  1. N Engl J Med v.314 An adoption study of human obesity Stunkard AJ;Sorensen TI;Hanis C;Teasdale TW;Chakraborty R;Schull WJ;Schulsinger F https://doi.org/10.1056/NEJM198601233140401
  2. Annu Rev Nutr v.13 Genetics of obesity Bouchard C;Perusse L https://doi.org/10.1146/annurev.nu.13.070193.002005
  3. N Engl J Med v.333 Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic receptor gene Walston J;Silver K;Bogardus C;Knowler W;Celi FS;Austin S;Manning B;Strosberg AD;Stern MP;Raben N https://doi.org/10.1056/NEJM199508103330603
  4. Diabetes v.46 Polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns Sipilainen R;Uusitupa M;Heikkinen S;Rissanen A;Laakso M https://doi.org/10.2337/diabetes.46.1.77
  5. J Intern Med v.247 The Q/E27 polymorphism in the beta2-adrenoceptor gene is associated with increased body weight and dyslipoproteinaemia involving triglyceride-rich lipoproteins Ehrenborg E;Skogsberg J;Ruotolo G;Large V;Eriksson P;Arner P;Hamsten A https://doi.org/10.1046/j.1365-2796.2000.00669.x
  6. Br J Pharmacol v.117 In situ assessment of the role of the beta 1-, beta 2- and beta 3- adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue Barbe P;Millet L;Galitzky J;Lafontan M;Berlan M https://doi.org/10.1111/j.1476-5381.1996.tb15279.x
  7. J Clin Endocrinol Metab v.54 Relation of body fat distribution to metabolic complications of obesity Kissebah AH;Vydelingum N;Murray R;Evans DJ;Hartz AJ;Kalkhoff RK;Adams PW https://doi.org/10.1210/jcem-54-2-254
  8. Metabolism v.36 Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity Fujioka S;Matsuzawa Y;Tokunaga K;Tarui S https://doi.org/10.1016/0026-0495(87)90063-1
  9. N Engl J Med v.333 Genetic variation in the beta3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity Clement K;Vaisse C;Manning BS;Basdevant A;Guy Grand B;Ruiz J;Silver KD;Shuldiner AR;Froguel P;Strosberg AD https://doi.org/10.1056/NEJM199508103330605
  10. Diabetes v.45 Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the beta3-adrenergic receptor gene Urhammer SA;Clausen JO;Hansen T;Pedersen O https://doi.org/10.2337/diabetes.45.8.1115
  11. J Clin Endocrinol Metab v.77 Lack of beta3-adrenergic effect on lipolysis in human subcutaneous adipose tissue Rosenbaum M;Malbon CC;Hirsch J;Leibel RL https://doi.org/10.1210/jc.77.2.352
  12. Diabetologia v.39 Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain Fujisawa T;Ikegami H;Yamato E;Takekawa K;Nakagawa Y;Hamada Y;Oga T;Ueda H;Shintani M;Fukuda M;Ogihara T https://doi.org/10.1007/BF00418352
  13. Hum Genet v.101 Trp64Arg beta3-adrenergic receptor and obesity in Mexican Americans Silver K;Mitchell BD;Walston J;Sorkin JD;Stern MP;Roth J;Shuldiner AR https://doi.org/10.1007/s004390050633
  14. Diabetes Care v.20 The Trp64Arg polymorphism of the beta 3-Adrenergic receptor gene. Lack of association with NIDDM and features of insulin resistance syndrome Rissanen J;Kuopusjarvi J;Pihlajamaki J;Sipilainen R;Heikkinen S;Vanhala M;Kekalainen P;Kuusisto J;Laakso M https://doi.org/10.2337/diacare.20.8.1319
  15. J Clin Endocrinol Metab v.81 Role of the beta3-adrenergic receptor locus in obesity and non insulin-dependent diabetes among members of Caucasian families with a diabetic sibling pair Elbein S.;Hoffman M;Barrett K;Wegner K;Miles C;Bachman K;Berkowitz D;Shuldiner AR;Leppert MF;Hasstedt S https://doi.org/10.1210/jc.81.12.4422
  16. Diabetologia v.42 The W64R variant of the beta3-adrenergic receptor is not associated with type Ⅱ diabetes or obesity in a large Finnish sample Ghosh S;Langefeld CD;Ally D;Watanabe RM;Hauser ER;Magnuson VL;Nylund SJ;Valle T;Eriksson J;Bergman RN;Tuomilehto J;Collins FS;Boehnke M https://doi.org/10.1007/s001250051144
  17. Biochem Biophys Res Commun v.258 The Gln27Glu beta2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men Mori Y;Kim Motoyama H;Ito Y;Katakura T;Yasuda K;Ishiyama Shigemoto S;Yamada K;Akanuma Y;Ohashi Y;Kimura S;Yazaki Y;Kadowaki T https://doi.org/10.1006/bbrc.1999.0607
  18. J Intern Med v.245 The different effects of a Gln27Glu beta2-adrenoceptor gene polymorphism on obestiy in males and in females Hellstrom L;Large V;Reynisdottir S;Wahrenberg H;Arner P https://doi.org/10.1046/j.1365-2796.1999.0437e.x
  19. Diabetologia v.42 Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertrigly ceridaemia, and diabetes mellitus Ishiyama-Shigemoto S;Yamada K;Yuan X;Ichikawa F;Nonaka K https://doi.org/10.1007/s001250051120
  20. J lin Invest v.100 Human beta -2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function Large V;Hellstrom L;Reynisdottir S;Lonnqvist F;Eriksson P;Lannfelt L;Arner P https://doi.org/10.1172/JCI119854
  21. N Engl J Med v.333 Association of a polymorphism in the beta3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns Widen E;Lehto M;Kanninen T;Walston J;Shuldiner AR;Groop LC https://doi.org/10.1056/NEJM199508103330604
  22. J Clin Invest v.98 The Trp64Arg mutation of the beta 3 adrenergic receptor gene has no effect of obesity phenotypes in the Quebec Family Study and Swedish Obese Subjects cohorts Gagnon J;Mauriege P;Roy S;Sjostrom D;Chagnon YC;Dionne FT;Oppert JM;Perusse L;Sjostrom L;Bouchard C https://doi.org/10.1172/JCI119014
  23. Diabetes Care v.20 Report of the expert committee on the diagnosis and classification of diabetes mellitus https://doi.org/10.2337/diacare.20.7.1183
  24. Korean J Nutr v.35 Comparative analysis of obesity by beta-2, 3 adrenergic receptor gene polymorphism in Korean young females Hong JM;Ahn HS;Kim JH;Park YS;Choi SM;Yoon YS
  25. Metabolism v.51 Significance of beta2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects Kim SH;Kim DJ;Seo IA.;Min YK;Lee MS;Kim KW;Lee MK https://doi.org/10.1053/meta.2002.33347
  26. Clin Chim Acta v.274 Association of the Trp64Arg mutation of the beta3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects Shima Y;Tsukada T;Nakanishi K;Ohta H https://doi.org/10.1016/S0009-8981(98)00059-X
  27. Diabetologia v.40 Beta 3-adrenergic-receptor polymorphism: a genetic marker for visceral fat obesity and the insulin resistane syndrome Sakane N;Yoshida T;Umekawa,T;Kondo M;Sakai Y;Takahashi T https://doi.org/10.1007/s001250050663
  28. Diabetes v.50 Identifiation of an interactive effect of beta3-and alpha2b-adrenoceptor gene polymorphisms on fat mass in Caucasian women Dionne IJ;Turner AN;Tchernof A;Pollin TI;Avrithi D;Gray D;Shuldiner AR;Poehlman ET https://doi.org/10.2337/diabetes.50.1.91
  29. J Clin Endocrinol Metab v.83 The Trp64Arg polymorphism of the β3-adrenergic receptor gene is not associated receptor gene is not associated with obesity or type 2 diabetes mellitus in a large population based Caucasian cohort Buettner R;Schaffler A;Arndt H;Rogler G;Nusser J;Zietz B;Enger I;Hugl S;Cuk A;Scholmerich J;Palitzsch KD https://doi.org/10.1210/jc.83.8.2892
  30. Kor Assoc Inter Medicine v.53 Sigificance of β3-adrenergic receptor gene polymorphism in the pathogenesis of NIDDM in Koreans Ahn KJ;Kim KA.;Kim YS;Choung JH;Koh EM;Min YK;Lee MS;Lee MK;Kim JW;Kim KW
  31. Diabetologia v.40 A mutation of the beta3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride Kim-Motoyama H;Yasuda K;Yamaguchi T;Yamada N;Katakura T;Shuldiner AR;Akanuma Y;Ohashi Y;Yazaki Y;Kadowaki T https://doi.org/10.1007/s001250050702
  32. Diabetes Care v.20 Effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients Sakane N;Yoshida T;Umekawa T;Kogure A;Takakura Y;Kondo M https://doi.org/10.2337/diacare.20.12.1887
  33. Biochem Biophys Res Commun v.215 A mutation in the beta3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects Kadowaki H;Yasuda K;Iwamoto K;Otabe S;Shimokawa K;Silver K;Walston J;Yoshinaga H;Kosaka K;Yamada N https://doi.org/10.1006/bbrc.1995.2500
  34. Metabolism v.48 Association of beta3-adrenergic receptor gene polymorphism with insulin resistance in Japanese-American men Kawamura T;Egusa G;Okubo M;Imazu M;Yamakido M https://doi.org/10.1016/S0026-0495(99)90145-2
  35. Metabolism v.47 The Trp64Arg mutation of the beta3-adrenergic receptor is associated with hyperglycemia and current body mass index in Jamaican women McFarlane-Anderson N;Bennett F;Wilks R;Howell S;Newsome C;Cruickshank K;Forrester T https://doi.org/10.1016/S0026-0495(98)90249-9
  36. Metabolism v.48 Relation of beta3-adrenergic receptor gene mutation to total body fat but not percent body fat and insulin levels in Thais Ongphiphadhanakul B;Rajatanavin R;Chanprasertyothin S;Piaseu N;Chailurkit L;Komindr S;Bunnag P;Puavilai G https://doi.org/10.1016/S0026-0495(99)90051-3
  37. Diabetologia v.40 No effect of the Trp64Arg beta 3-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue Snitker S;Odeleye OE;Hellmer J;Boschmann M;Monroe MB;Shuldiner AR;Ravussin E https://doi.org/10.1007/s001250050757
  38. Metabolism v.47 The significance of the Trp 64 Arg mutation of the beta 3 adrenergic receptor gene in impaired glucose tolerance, non-insulin dependent diabetes mellitus, and insulin resistance in Japanese subjects Azuma N;Yoshimasa Y;Nishimura H;Yamamoto Y;Masuzaki H;Suga J;Shigemoto M;Matsuoka N;Tanaka T;Satoh N;Igaki T;Miyamoto Y;Itoh H;Yoshimasa T;Hosoda K;Nish S;Kakao K https://doi.org/10.1016/S0026-0495(98)90059-2
  39. Arterioscler Thromb Vasc Biol v.18 Clinical features associated with the homozygous Trp64Arg mutation of the beta3 adrenergic receptor: no evidence for its association with obesity in Japanese Sun L;Ishibashi S;Osuga J;Harada K;Ohashi K;Gotoda T;Fukuo Y;Yazaki Y;Yamada N https://doi.org/10.1161/01.ATV.18.6.941
  40. Diabetologia v.40 Beta 3-adrenergic receptor gene variant and lipid metabolism in Pima Indians Tataranni PA;Pratley R;Shuldiner A;Ravussin E https://doi.org/10.1007/s001250051425